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Title: Small-molecule inhibitors of mTOR and DNA-PK
Author: Payne, Sara Lauren
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2010
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The phosphatidylinositol-3-kinase related kinase (PIKK) family of proteins consists of five serine-threonine protein kinase members (ATM, ATR, hSMG, DNA-PK and mTOR), each of which have been implicated in the cellular response to DNA damage or cellular stress. Upregulation of the PBKJAKT cell signalling pathway has been demonstrated to be a common driver of malignancy in human cancer. The mammalian target of rapamycin (mTOR) exists in two isoforms, both of which lie within the PBKJAKT pathway and as such are capable of mediating the activity of the signalling pathway. The first reported inhibitor of mTOR was rapamycin, a macrocylic lactone which acts an allosteric inhibitor of the mTORCI complex only. Subsequent drug discovery efforts have been focussed upon the development of ATP-competitive inhibitors of mTOR, which would facilitate the inhibition of both mTOR complexes thereby interrupting the P13K/AKT pathway at two distinct points.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available